Tea Leaves: Predicting Risk and Benefit in Translation

by


Every early phase trial begins with a series of predictions: that a new drug will show clinical utility down to road, that risks to study volunteers will be manageable, and perhaps, that patients in trials will benefit. Make a bad prediction here, and people potentially get hurt and resources wasted. So how good a job do we do with these predictions?


Hard to know, but given the high rate of failure in clinical translation, there are grounds for believing that various stakeholders go into early phase trials with an excess of optimism. In the current issue of PLoS Medicine, Alex London and I posit two problems with the way decision-makers make predictions in early phase trials. First, they underattend frequent and systematic flaws in the preclinical evidence base. Secondly, they draw on an overly narrow evidence base (what we call “evidential conservatism”) that obscures an assessment of whether preclinical studies in a given research area are a reliable indicator of agent promise.

As an open access journal, readers are invited to view our article here. The article has garnered a decent amount of press- digestible summaries can also be found at the Scientist and Pittsburgh Gazette. Also check out a commentary commissioned by the journal editors. (photo credit: canopic 2010)

BibTeX

@Manual{stream2011-54,
    title = {Tea Leaves: Predicting Risk and Benefit in Translation},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2011,
    month = mar,
    day = 21,
    url = {http://www.translationalethics.com/2011/03/21/tea-leaves-predicting-risk-and-benefit-in-translation/}
}

MLA

Jonathan Kimmelman. "Tea Leaves: Predicting Risk and Benefit in Translation" Web blog post. STREAM research. 21 Mar 2011. Web. 21 Sep 2017. <http://www.translationalethics.com/2011/03/21/tea-leaves-predicting-risk-and-benefit-in-translation/>

APA

Jonathan Kimmelman. (2011, Mar 21). Tea Leaves: Predicting Risk and Benefit in Translation [Web log post]. Retrieved from http://www.translationalethics.com/2011/03/21/tea-leaves-predicting-risk-and-benefit-in-translation/


ASGCT, cont’: Results on Fetal Tissue for Battens Presented

by

Robert Steiner, co-principal investigator in a fetal cell transplantation study involving the rare, fatal hereditary disease Neuronal Ceroid Lipofuscinosis (also known as Batten disease), presented results of a now completed phase 1 study. According to Steiner, the study involved the highest ever dose of stem cells delivered to the human brain. The trial involved six children with infantile and late-infantile forms of the disease.


Elsewhere, this safety study has been reported as “positive”- in the sense that there were no unexpected, stem cell related complications. Which is not to say the protocol was a picnic: the study involved (if I understood the presentation correctly) 14 trajectories to the brain, and an extended regime of immunosuppression that caused 23 adverse events. Steiner reported that none of the patients showed a clinical response- which is what one would expect in patients with such advanced forms of disease (hopefully, the research team conveyed the unexpectedness of clinical benefits to parents when they obtained informed consent).

Steiner also reported that, when one of the patients died due to natural course of illness, the family permitted the team to perform an autopsy. The autopsy ruled out the cell transplantation as a cause of mortality, and established that the tissues engrafted successfully. In the words of a press release, “By permitting the autopsy, the family allowed the researchers to learn very important details that will potentially benefit future patients.”

Did the research team use the autopsy to determine whether the transplanted cells were expressing the therapeutic gene? If so, was the gene product taken up by surrounding tissues? Answering these questions would be key to maximizing the scientific value of the study, and thus redeeming the risks of surgery, immunosuppression, stem cell transplantation, and the many follow-up visits required of patients participating in the study. But from what I heard, the brain is in the hands of the company, and it is unclear whether they have performed these studies (and if so, whether the results will be reported). Let’s hope the family’s permission for autopsy allows the researchers to learn still more. (photo credit: dopamineharper 2009)

BibTeX

@Manual{stream2010-62,
    title = {ASGCT, cont’: Results on Fetal Tissue for Battens Presented},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2010,
    month = may,
    day = 26,
    url = {http://www.translationalethics.com/2010/05/26/asgct-cont-results-on-fetal-tissue-for-battens-presented/}
}

MLA

Jonathan Kimmelman. "ASGCT, cont’: Results on Fetal Tissue for Battens Presented" Web blog post. STREAM research. 26 May 2010. Web. 21 Sep 2017. <http://www.translationalethics.com/2010/05/26/asgct-cont-results-on-fetal-tissue-for-battens-presented/>

APA

Jonathan Kimmelman. (2010, May 26). ASGCT, cont’: Results on Fetal Tissue for Battens Presented [Web log post]. Retrieved from http://www.translationalethics.com/2010/05/26/asgct-cont-results-on-fetal-tissue-for-battens-presented/


Disclosure in Phase 1 Cancer Trials

by

Followers of this blog may recall my continuing concern with the way informed consent is obtained in phase 1 trials involving patient-volunteers (typically, these patients have exhausted standard care options and enter phase 1 trials as a final shot at managing their disease). Language used by investigators in these studies is often suggestive of therapeutic benefit, even though meta-analyses of phase 1 studies show that chances of major clinical benefit in phase 1 studies are exceedingly low. In previous posts, I described my own experience with an ethics review committee that actually defended giving patients vague and almost meaningless information about the therapeutic benefits of phase 1 trial participation. Meantime, evidence from surveys indicate that phase 1 cancer patient-volunteers tend to overestimate the probability of therapeutic benefit.


In the July-August 2009 edition of the ethics journal IRB, Shlomo Koyfman and co-authors at NIH offer up a “Consent Form Template for Phase I Oncology Trials.” Their recommendations are comprehensive and excellent. Among the items they recommend are:

• use of more therapeutically neutral language, like “research agent” instead of “therapy”

• disclosure of dose escalation design; in particular, the authors recommend that patients be informed about risks and benefits relative to the cohort they are entering.

• a statement (where appropriate) that patient-volunteers will not have the option of adjusting their dose assignment in the study

• a statement that “the chances that this agent will… allow you to live longer [is] very low.”

One can quibble with various particulars (I think, for example, discussion of subtherapeutic dosing should be more explicit). But on the whole, these recommendations provide an excellent standard– along with NIH Guidance on Informed Consent for Gene Transfer Research– against which typical phase 1 cancer study consent forms should be measured. (photo credit: banlon1964)

BibTeX

@Manual{stream2009-83,
    title = {Disclosure in Phase 1 Cancer Trials},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = oct,
    day = 26,
    url = {http://www.translationalethics.com/2009/10/26/disclosure-in-phase-1-cancer-trials/}
}

MLA

Jonathan Kimmelman. "Disclosure in Phase 1 Cancer Trials" Web blog post. STREAM research. 26 Oct 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/10/26/disclosure-in-phase-1-cancer-trials/>

APA

Jonathan Kimmelman. (2009, Oct 26). Disclosure in Phase 1 Cancer Trials [Web log post]. Retrieved from http://www.translationalethics.com/2009/10/26/disclosure-in-phase-1-cancer-trials/


by

Who says the British Press isn’t all yellow?  “Doctors have begun trials using gene therapy to treat patients for cystic fibrosis.”  So proclaims an April 19 story in the Guardian (“Cystic fibrosis to be treated by gene therapy technology”).  “Cystic fibrosis gene cure closer,” reads a Februrary 2009 BBC headline.

Details available
“‘We are not curing the condition,’ stressed scientist Dr. Deborah Gill. ‘We will merely be halting the erosion of patients’ lung function.'”(photo credit: Lisabuddka 2008)

BibTeX

@Manual{stream2009-101,
    title = {},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = may,
    day = 15,
    url = {http://www.translationalethics.com/2009/05/15/101/}
}

MLA

Jonathan Kimmelman. "" Web blog post. STREAM research. 15 May 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/05/15/101/>

APA

Jonathan Kimmelman. (2009, May 15). [Web log post]. Retrieved from http://www.translationalethics.com/2009/05/15/101/


Basic Science and Pharmaceutical Productivity

by

One of the great paradoxes of contemporary medicine has been a seeming inverse relationship between investment in basic science and registration of novel new drugs by regulatory agencies. The delay between basic science discoveries and clinical applications can be very long; many promising drug candidates are called on the basis of laboratory discovery, but few are chosen.


Cancer drugs, in particular, have one of the highest rates of failure as measured by the probability that a new drug entering phase 1 clinical testing will prove promising enough to eventually be registered by the FDA. One 2004 report pegged this figure at about 5%.

The question is: will such discouragingly low figures hold for new classes of cancer drugs that are entering clinical testing? According to Ian Walker and Herbie Newell in the January issue of Nature Reviews Drug Discovery, maybe not. Walter and Newell examined pharmaceutical development databases to determine probabilities that a particular class of new cancer drugs– protein kinase inhibitors– will survive from phase 1 testing through to registration (the wonder drug Gleevec is in this class). They found that 53% of new kinase inhibitors that enter phase 1 trials are ultimately licensed. They conclude that their analysis “further demonstrate[s] the benefits of developing molecularly targeted therapeutics for cancer.”

Here are some concerns about their analysis. First, their figures for success from phase 1 to registration for all cancer drugs (not just kinase inhibitors) are roughly three times previous estimates. This bears explaining. A second concern is that this may represent a particularly successful class of molecularly targeted agents. Third and crucially, according to a recent Nature Reviews–Cancer report, there are 11 different kinase inhibitors approved by the FDA. Eleven divided by the sample used in this paper– 137 kinase inhibitor drugs entering phase 1 testing– yields 8%– a number very similar to the 5% success rate that has been quoted elsewhere. Last, some kinase inhibitors are “me-toos” or at least, very closely related (e.g. panitumumab and cetexumab)

Too early, I say, to conclude that the way we are doing basic and preclinical science is beginning to bear fruit in terms of pharmaceutical productivity. (photo credit: Night Heron, Pull Chain, 2007)

BibTeX

@Manual{stream2009-102,
    title = {Basic Science and Pharmaceutical Productivity},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = may,
    day = 13,
    url = {http://www.translationalethics.com/2009/05/13/basic-science-and-pharmaceutical-productivity/}
}

MLA

Jonathan Kimmelman. "Basic Science and Pharmaceutical Productivity" Web blog post. STREAM research. 13 May 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/05/13/basic-science-and-pharmaceutical-productivity/>

APA

Jonathan Kimmelman. (2009, May 13). Basic Science and Pharmaceutical Productivity [Web log post]. Retrieved from http://www.translationalethics.com/2009/05/13/basic-science-and-pharmaceutical-productivity/


Departing Milano Stazione? ADA-SCID and Gene Transfer

by

Greetings after a hiatus for teaching, grants, committees, book deadlines, wiping runny noses, and more. Much has happened since my last posting, and in the next two or three weeks, I hope to catch up.


First item on the agenda is a Jan 29 report in New England Journal of Medicine (NEJM) describing successful reconstitution of immune function in eight of ten children receiving gene transfer for adenosine deaminase severe combined immune deficiency (ADA-SCID). The paper follows on a previous report in Science, 2002, and almost certainly counts as gene transfer’s greatest clinical accomplishment to date.

I have previously argued in Lancet and Developing World Bioethics, as well as in my forthcoming book, that this study raised important justice concerns because it recruited volunteers from economically disadvantaged settings without clearly fulfilling the requirement, articulated in the Declaration of Helinki, of responsiveness. The NEJM article does not say where subsequent volunteers were recruited, though the fact that all but one new volunteer received PEG-ADA (a very expensive standard of care available only in high-income countries) suggests that later patients were not economically disadvantaged.

Rather than dwell on justice, I’d like to focus on the significance of this study. As indicated, eight of ten children with a life threatening immune disorder had their immune systems reconstituted. Five of these children had T-cell counts that were “above the lower limits of normal.” These children were able to enjoy normal social relations parents and other children.

There do not appear to have been any adverse events relating to the gene transfer vector. A major concern was the possibility that gene transfer might trigger a leukemia-like syndrome observed in two X-SCID studies. Blood tests of children in this ADA-SCID study, however, do not evidence of either the leukemia syndrome or its precursors– at least within the time frame of the study (median follow-up of 4 years; range: 1.8-8 years).

So is ADA-SCID gene transfer ready to leave Milan and conquer ADA-SCID?  For children lacking haplo-identical bone marrow donors, maybe so given the morbidity associated with marrow  transplantation. Still, there are lingering concerns. First, though these results are encouraging, risks of malignancy remain unquantified. Second, this gene transfer regime requires several ancillary treatments- like bone marrow conditioning- that expose patients to risk of infection until the gene transfer intervention kicks in. Several volunteers in this study developed infections and neutropenia, for example. In an accompanying editorial in NEJM, Donald Kohn and Fabio Candotti describe several ways that retroviral gene transfer to blood stem cells might be made safer. Last, it is important to remember that ADA-SCID is a multi-system disorder, with neurological, skeletal, and other effects. Though this approach seems to address what is by far the largest cause of morbidity and mortality in children with ADA-SCID, it does eradicate their condition.

The results of Aiuti et al have been widely celebrated in the gene transfer community.  Kohn and Candotti’s editorial, for example, is titled “Gene Therapy Fulfilling its Promise.”  More than any single gene transfer study I can think of, this one seems to have earned the vindicating headlines. (photo credit: Paolo Margari, Milano Sazione Centrale Ferrovi, 2008)

BibTeX

@Manual{stream2009-109,
    title = {Departing Milano Stazione? ADA-SCID and Gene Transfer},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = mar,
    day = 10,
    url = {http://www.translationalethics.com/2009/03/10/departing-milano-stazione-ada-scid-and-gene-transfer/}
}

MLA

Jonathan Kimmelman. "Departing Milano Stazione? ADA-SCID and Gene Transfer" Web blog post. STREAM research. 10 Mar 2009. Web. 21 Sep 2017. <http://www.translationalethics.com/2009/03/10/departing-milano-stazione-ada-scid-and-gene-transfer/>

APA

Jonathan Kimmelman. (2009, Mar 10). Departing Milano Stazione? ADA-SCID and Gene Transfer [Web log post]. Retrieved from http://www.translationalethics.com/2009/03/10/departing-milano-stazione-ada-scid-and-gene-transfer/


Northern Lights? Canada and the New Tricouncil Draft

by

Since it’s issuance in 1998, Canada’s Tricouncil Policy Statement (Canada’s policy on the ethics of human research) has had an influence on the practice of research ethics that has outsized Canada’s population.  The three research councils– CIHR, NSERC, and SSHRC– are presently revising the Tricouncil, and a few days ago, a revised draft was presented on the CIHR web site.  


There is much to commend the newest version.  There are also a number of disappointments. I won’t dwell on these here, however. Instead, I will focus on Tricouncil’s revised language on phase 1 and gene transfer research.

The revised Tricouncil contains a definition of phase 1 that, in my view, is somewhat outmoded and not much of an improvement on the old version. Both emphasize the role of phase 1 in toxicity and dose determination, but do not encompass the many other purposes to which phase 1 trials are put (e.g. for deciding whether to pursue phase 2, for gathering evidence of biological effects, etc.).  On the other hand, the new Tricouncil requires prospective registration of all trials– including phase 1. And it contains a lengthy discussion of “therapeutic misconception,” which it defines as “the tendency of trial participants to believe that the primary intention of research tests and interventions is to provide a therapeutic benefit to the patient-participant.”  The document urges research ethics boards and researchers to “emphasize  which specific elements  of a clinical study are required for research purposes, as well as the differences between research and the standard clinical care they might otherwise receive.”  Bravo.

The new Tricouncil also, for the most part, replaces the old language of “gene therapy” with the more neutral “gene transfer.”  In a section on “Gene Transfer,” the new draft warns about therapeutic misconception. It shrinks from any ethical statement on germline modification by deferrinng to Canada’s Assisted Human Reproduction Act.  The remainder of the text notes the irreversibility of genetic alterations (not quite accurate), the potentially latent nature of gene transfer risks (a point I agree with), and states that research and ethical debate is evolving rapidly (a point I mostly agree with). Somewhat disappointingly, there is no mention of the need for centralized, transparent, or specialized review of such protocols.

On balance, these two sets of modifications are pretty good, though rather than anticipate the issues that are likely to arise in the next 5-10 years while this draft is in force, I worry a little that instead the draft represents a policy that I and others wish we might have had in the previous 5-10 years. Onwards and upwards! (photo credit: Studiolit 2006)

BibTeX

@Manual{stream2008-118,
    title = {Northern Lights? Canada and the New Tricouncil Draft},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = dec,
    day = 8,
    url = {http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/}
}

MLA

Jonathan Kimmelman. "Northern Lights? Canada and the New Tricouncil Draft" Web blog post. STREAM research. 08 Dec 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/>

APA

Jonathan Kimmelman. (2008, Dec 08). Northern Lights? Canada and the New Tricouncil Draft [Web log post]. Retrieved from http://www.translationalethics.com/2008/12/08/northern-lights-canada-and-the-new-tricouncil-draft/


Ethics, Phase 1 Trials, and the Developing World

by

Under what conditions is it ethical to perform phase 1, translational clinical trials in low and middle-income countries? Together with lead author Alex John London (Carnegie Mellon, Philosophy), I attempt to answer that question in the July 5 issue of Lancet (“Justice in Translation: From Bench to Bedside in the Developing World”).


The article makes three main points. First, we note that much discussion about international research has centered on post-trial access to interventions (that is, should patients enrolled in trials be provided with free drug even after a trial is completed?) However, we argue that this question is irrelevant for phase 1 studies, which test safety rather than efficacy.

Second, we note that most major national and international ethics codes indicate that trials conducted in disadvantaged communities should be responsive to local health needs. We suggest that this is the appropriate standard for determining whether phase 1 trials are consistent with international standards of fairness for clinical research.

Third, we attempt to specify what international policies actually mean by responsiveness. We suggest that a trial is responsive if it addresses an urgent, umet health need of a host community, and if it is part of a process of developing knowledge that can reasonably be projected to be applied in a host community. (photo credit: VCU Tompkins-McCaw Library Collections, 2008)

BibTeX

@Manual{stream2008-144,
    title = {Ethics, Phase 1 Trials, and the Developing World},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = jul,
    day = 22,
    url = {http://www.translationalethics.com/2008/07/22/ethics-phase-1-trials-and-the-developing-world/}
}

MLA

Jonathan Kimmelman. "Ethics, Phase 1 Trials, and the Developing World" Web blog post. STREAM research. 22 Jul 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/07/22/ethics-phase-1-trials-and-the-developing-world/>

APA

Jonathan Kimmelman. (2008, Jul 22). Ethics, Phase 1 Trials, and the Developing World [Web log post]. Retrieved from http://www.translationalethics.com/2008/07/22/ethics-phase-1-trials-and-the-developing-world/


Are Phase 1 Volunteers Vulnerable?

by

In the January 2008 issue of Archives of Internal Medicine, an NIH team led by Christine Grady reports the results of a study (Participants in Phase 1 Oncology Research Trials: Are They Vulnerable?) surveying the demographics of patients who participate in phase 1 cancer studies. They report that these volunteers are overwhelmingly white, have pretty good physical functioning, earn above average incomes, have above average educational attainment, and do not lack for health insurance coverage. The authors then suggest that phase 1 volunteers “do not fit into any of the categories of vulnerable populations addressed by specific regulations.”


This is an informative paper, though the results should not surprise anyone who has followed the field of phase 1 cancer research. Their use of National Cancer Institute (NCI) data is clever and comprehensive (though their anemic sample of 11 non-NCI studies is puzzling). And I agree with the tacit message: that regulators and ethicists should avoid infantalizing persons with terminal illness.

On the other hand, the article contains some misleading or debatable statements. The suggestion that phase 1 cancer volunteers “do not fit into any categories of vulnerable populations” is not exactly true: the Belmont Report implicitly categorizes the “very sick” as vulnerable. The World Health Organizations CIOMS policy states quite clearly: “Persons who have serious, potentially disabling or life-threatening diseases are highly vulnerable.”

The view of vulnerability and autonomy espoused in this paper will strike many readers as thin and reductionistic– as if it were a box on a census form rather than an experience. So too is the suggestion that phase 1 study participants are not “in need of special protection.” Nevertheless, this paper does help direct our concerns away from income and demography towardvariables that might really matter, like dependence, fear, and flux. (photo credit: Lutz-R.Frank 2007).

BibTeX

@Manual{stream2008-145,
    title = {Are Phase 1 Volunteers Vulnerable?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = jul,
    day = 3,
    url = {http://www.translationalethics.com/2008/07/03/are-phase-1-volunteers-vulnerable/}
}

MLA

Jonathan Kimmelman. "Are Phase 1 Volunteers Vulnerable?" Web blog post. STREAM research. 03 Jul 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/07/03/are-phase-1-volunteers-vulnerable/>

APA

Jonathan Kimmelman. (2008, Jul 03). Are Phase 1 Volunteers Vulnerable? [Web log post]. Retrieved from http://www.translationalethics.com/2008/07/03/are-phase-1-volunteers-vulnerable/


On Not Getting It…

by



Here is the scenario: you have cancer, and your doctor has told you there is no way to treat it. But there is an experimental drug that is being offered in a phase 1 study. Your doctor asks if you’re interested.


You join the study because its your best shot. You know there are likely to be side effects–there always are with cancer drugs. You know the drug might not work–no cancer drug works all the time for all people.

If your doctor knew that entering the phase 1 study was unlikely to eradicate your cancer– or even extend your life– would you want to be told, or would you prefer that the doctor keep this information from you?

The question came up in a recent research ethics committee (IRB) meeting I attended, in which a phase 1 cancer study consent form contained language to the effect of “you may or may not benefit from joining this study.” I proposed that the language be changed to “this study is unlikely to significantly affect the course of your cancer.” My preference was based on the following reasons:

1- “may or may not benefit” does not contain any information about probability. Indeed, there is a subtle rhetorical partity, wherebt most readers view “may” as having equal weight as “may not” such that they view this as suggesting a 50% probability of benefit.

2- two recent, large mete-analyses showed that studies of the type reviewed here result in tumor shrinkage for about 10% of patients. There is no evidence that tumor shrinkage in these studies actually translates to longer life or improved comfort. So, in fact, we do have information about probability of benefit.

3- Patients enter these studies not because of a desire to further cancer research, but rather, because they are seeking cure. This has been shown in numerous surveys.

4- Patients who enter these studies significantly overestimate the probability that they will benefit clinically. Also shown in numerous surveys.

5- Informed consent requires, at a minimum, that volunteers be provided information that a reasonable person would consider material to their decision to enroll.

A reasonable, terminal cancer patient would probably want to have some information about the probability that a drug that is likely to have strong side effects is unlikely to work against their cancer.

Incredibily, most of the members of my IRB disagreed, saying (among other things) that it would discourage patients (hmmm. I thought medical paternalism went out with Buicks with tailfins); that nothing in the original language implied benefit was a sure thing (yes, the original language made it very clear that instead of 100% chance of benefit, chance of benefit was somewhere between 0 and 99.999%);  that no one would enroll in the study with my language (wow! I thought our job was to protect volunteers, not investigators); that we’ve never done that before (let me make sure I understand this.  It’s ok to withhold relevant information from volunteers, as long as you’ve done it before).

Yes, Virginia, the IRB system really is broken! (photo credit: Kenoir 2007)

BibTeX

@Manual{stream2008-146,
    title = {On Not Getting It…},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = jun,
    day = 27,
    url = {http://www.translationalethics.com/2008/06/27/on-not-getting-it/}
}

MLA

Jonathan Kimmelman. "On Not Getting It…" Web blog post. STREAM research. 27 Jun 2008. Web. 21 Sep 2017. <http://www.translationalethics.com/2008/06/27/on-not-getting-it/>

APA

Jonathan Kimmelman. (2008, Jun 27). On Not Getting It… [Web log post]. Retrieved from http://www.translationalethics.com/2008/06/27/on-not-getting-it/


Search STREAM

Old blog posts


All content © STREAM research

admin@translationalethics.com
Twitter: @stream_research
3647 rue Peel
Montreal QC H3A 1X1